Methods will be developed for maintenance of stable blood levels of barbiturates in mice, probably by subcutaneous implantation of pellets of barbital or pentobarbital, and for quantitative assessment of withdrawal signs when barbiturate administration is discontinued. We will study dose- and time-relationships in the development of physical dependence, and we will then be able to predict in numerical terms the severity of withdrawal reactions after a standard regimen of barbiturate administration. We will look for genetic and pharmacological factors that modify these relationships, i.e. factors that affect vulnerability to physical dependence. Cross-dependence with alcohol will be studied, again quantitatively, and the results throughout this project will be compared with those of our current studies on alcohol physical dependence in mice.